It is proposed to undertake detailed electron microscopical analyses of the aqueous outflow system, with special emphasis on the subcellular morphology of the lining endothelium of Schlemm's canal and juxtacanalicular tissue, in normal and glaucomatous human eyes; monkey eyes will be used as an experimental animal model, to provide control data. Investigations will be carried out to correlate the morphological response of the system with the physiological data at graded levels of intraocular pressure with or without intracameral perfusion experiments and the use of tracer substances. The role of the hydrostatic pressure gradient in influencing the morphological adaptation of the system will be clarified and analysis will be made, by electron microscopy and immunofluorescent techniques with or without the use of pharmacologically active substances, of the cytoskeletal system and any special property of the cells lining Shlemm's canal, and the changes in the juxtacanalicular tissue. Thus the factors responsible for the formation of macrovacuolar structures seemingly providing the final pathway for the bulk outflow of aqueous humour across the endothelial barrier of Shlemm's canal will be defined. The pathological changes in human eyes with chronic simple glaucoma will also be studied by electron microscopy and immunofluorescent techniques. The overall aim is to enhance the understanding of the physiopathology of aqueous humour outflow system and the pathogenesis of chronic simple glaucoma.